Compositions and methods for treatment of thyroid eye disease

Abstract

Antibodies and compositions against Insulin-Like Growth Factor-1 Receptor (IGF-1R) with extended half-lives and uses thereof are provided herein. Antibodies and compositions described herein can be used in methods of treating or reducing the severity of thyroid eye disease (TED) in subjects in need thereof, by inhibiting the activity of IGF-1R with such antibodies and compositions.

What is claimed is: 
     
         1 . A method of treating thyroid eye disease (TED) in a subject having TED and in need thereof, the method comprising administering an anti-IGF-1R antibody comprising a light chain and a heavy chain, wherein
 a) the light chain comprises a light chain variable region comprising a LCDR1 having an amino acid sequence of SEQ ID NO: 53, a LCDR2 having an amino acid sequence of SEQ ID NO: 54, and a LCDR3 having an amino acid sequence of SEQ ID NO: 55, and   b) the heavy chain comprises a heavy chain variable region and a Fc region, wherein the heavy chain variable region comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 56, a HCDR2 having an amino acid sequence of SEQ ID NO: 57, and a HCDR3 having an amino acid sequence of SEQ ID NO: 58, and the Fc region comprising M252Y, S254T, and T256E substitutions wherein numbering is according to the Kabat numbering system.   
     
     
         2 . The method of  claim 1 , wherein the anti-IGF-1R antibody is administered subcutaneously. 
     
     
         3 . The method of  claim 1 , wherein treating TED comprises reducing proptosis by at least 2 mm as measured by an exophthalmometer in one or both eyes of the subject. 
     
     
         4 . The method of  claim 1 , wherein treating TED comprises reducing a Clinical Activity Score (CAS) of the subject. 
     
     
         5 . The method of  claim 1 , wherein treating TED comprises reducing proptosis by at least 2 mm as measured by an exophthalmometer and reducing a clinical activity score (CAS) of the subject. 
     
     
         6 . The method of  claim 1 , wherein treating TED comprises reducing the severity of diplopia of the subject. 
     
     
         7 . The method of  claim 1 , wherein the light chain variable region comprises an amino acid sequence of SEQ ID NO: 13 and the heavy chain variable region comprises an amino acid sequence of SEQ ID NO: 14. 
     
     
         8 . The method of  claim 1 , wherein the light chain comprises an amino acid sequence of SEQ ID NO: 93 and the heavy chain comprises an amino acid sequence of SEQ ID NO: 94. 
     
     
         9 . A method of treating thyroid eye disease (TED) in a subject having TED and in need thereof, the method comprising administering to the subject an anti-IGF-1R antibody comprising a light chain and a heavy chain, wherein:
 a) the light chain comprises a LCDR1 having an amino acid sequence of SEQ ID NO: 53, a LCDR2 having an amino acid sequence of SEQ ID NO: 54, and a LCDR3 having an amino acid sequence of SEQ ID NO: 55; and   b) the heavy chain comprises a heavy chain variable region and a Fc region,   wherein the heavy chain variable region comprises a HCDR1 having an amino acid sequence of SEQ ID NO: 56, a HCDR2 having an amino acid sequence of SEQ ID NO: 57, and a HCDR3 having an amino acid sequence of SEQ ID NO: 58, and   wherein the Fc region comprises an amino acid sequence of SEQ ID NO: 89.   
     
     
         10 . The method of  claim 9 , wherein the anti-IGF-1R antibody is administered subcutaneously. 
     
     
         11 . The method of  claim 9 , wherein treating TED comprises reducing proptosis in one or both eyes of the subject. 
     
     
         12 . The method of  claim 9 , wherein treating TED comprises reducing a Clinical Activity Score (CAS) of the subject. 
     
     
         13 . The method of  claim 9 , wherein treating TED comprises reducing proptosis by at least 2 mm as measured by an exophthalmometer and reducing clinical activity score (CAS) of the subject. 
     
     
         14 . The method of  claim 9 , wherein treating TED comprises reducing the severity of diplopia of the subject. 
     
     
         15 . The method of  claim 9 , wherein the light chain variable region comprises an amino acid sequence of SEQ ID NO: 13 and the heavy chain variable region comprises an amino acid sequence of SEQ ID NO: 14. 
     
     
         16 . The method of  claim 2 , wherein the light chain variable region comprises an amino acid sequence of SEQ ID NO: 13 and the heavy chain variable region comprises an amino acid sequence of SEQ ID NO: 14. 
     
     
         17 . The method of  claim 2 , wherein the light chain comprises an amino acid sequence of SEQ ID NO: 93 and the heavy chain comprises an amino acid sequence of SEQ ID NO: 94. 
     
     
         18 . The method of  claim 10 , wherein the light chain variable region comprises an amino acid sequence of SEQ ID NO: 13 and the heavy chain variable region comprises an amino acid sequence of SEQ ID NO: 14.